The role of Class I HLA antigens in cell-cell interactions was studied. Rapid turnover of HLA proteins in human peripheral lymphocytes was inhibited by conditions that minimized cell-cell contact. HLA antigens in human platelets were phosphorylated under conditions of platelet aggregation. These findings suggest that HLA molecules are metabolically responsive to cell-cell and cell-environment interactions. Peripheral lymphocytes were shown to synthesize and secrete Calmodulin continuously. The secreted molecules may play a role in modulating cell-cell interactions. The biochemical basis for the genetic predisposition of NZB mice to autoimmune disease is being studied. A developmental derangement was found in expression of certain proteins by splenic lymphocytes in which proteins normally synthesized at high levels only in young animals were re-expressed as animals aged and developed autoimmune disease.